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Method: Allele-specific RNA N⁶-methyladenosine modifications reveal functional genetic variants in human tissues
- Shuo Cao,
- Haoran Zhu,
- Jinru Cui,
- Sun Liu,
- Yuhe Li,
- Junfang Shi,
- Junyuan Mo,
- Zihan Wang,
- Hailan Wang,
- Jiaxin Hu,
- Lizhi Chen,
- Yuan Li,
- Laixin Xia,
- and Shan Xiao
Genome Res. August 2023 33: 1369-1380; Published in Advance September 15, 2023, doi:10.1101/gr.277704.123
.... 2021). We hypothesized that an allele-specific m6A modification (ASm6A) analysis may greatly improve the accuracy and sensitivity of conventional MeRIP/m6A-seq assays (McIntyre et al. 2020), providing improved resolution of m6A quantification, especially in human tissue samples.In this study, we...
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Research: Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression
- Celine L. St. Pierre,
- Juan F. Macias-Velasco,
- Jessica P. Wayhart,
- Li Yin,
- Clay F. Semenkovich,
- and Heather A. Lawson
Genome Res. June 2022 32: 1042-1057; Published in Advance May 2, 2022, doi:10.1101/gr.276193.121
...-by-environment interactions can also alter gene expression patterns in a dynamic and tissue-specific manner without modifying the underlying nucleotide sequence; these effects are missed in a typical sequence-based method. Thus, an allele-specific approach is required to directly measure how cis-regulatory variation impacts...
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Method: Interpretation of allele-specific chromatin accessibility using cell state–aware deep learning
- Zeynep Kalender Atak,
- Ibrahim Ihsan Taskiran,
- Jonas Demeulemeester,
- Christopher Flerin,
- David Mauduit,
- Liesbeth Minnoye,
- Gert Hulselmans,
- Valerie Christiaens,
- Ghanem-Elias Ghanem,
- Jasper Wouters,
- and Stein Aerts
Genome Res. June 2021 31: 1082-1096; Published in Advance April 8, 2021, doi:10.1101/gr.260851.120
..., of which 15%–20% can be explained by gains or losses of transcription factor binding sites. A considerable fraction of ASCAVs are caused by changes in AP-1 binding, as confirmed by matched ChIP-seq data to identify allele-specific binding of JUN and FOSL1. Finally, by augmenting the DeepMEL2 model with Ch...
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Method: The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
- Daffodil M. Canson,
- Michael T. Parsons,
- Gemma Moir-Meyer,
- Troy Dumenil,
- Gemma Montalban,
- Erica Lin,
- Terri P. McVeigh,
- Aimee L. Davidson,
- Shaun M. Bouckaert,
- Matt Trau,
- Darren Korbie,
- and Amanda B. Spurdle
Genome Res. September 2025 35: 2104-2115; Published in Advance August 6, 2025, doi:10.1101/gr.279557.124
...of this empirical, hemizygous system are that it allows for allele-specific quantitative measurements of variant impact on splicing (Walker et al. 2023), permits assessment of cell-specific splicing effects by transient expression in different cell lines, and is easily scalable for high-throughput RNA analysis...
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Research: Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits
- Kevin W. Currin,
- Hannah J. Perrin,
- Gautam K. Pandey,
- Abdalla A. Alkhawaja,
- Swarooparani Vadlamudi,
- Annie E. Musser,
- Amy S. Etheridge,
- K. Alaine Broadaway,
- Jonathan D. Rosen,
- Arushi Varshney,
- Amarjit S. Chaudhry,
- Paul J. Gallins,
- Fred A. Wright,
- Yi-hui Zhou,
- Stephen C.J. Parker,
- Laura M. Raffield,
- Erin G. Schuetz,
- Federico Innocenti,
- and Karen L. Mohlke
Genome Res. July 2025 35: 1485-1502; Published in Advance May 20, 2025, doi:10.1101/gr.279741.124
...variant at the signal (LD r2 > 0.8) that overlapped a caPeak, which was the driver peak (peak273749). We tested 329 bp DNA elements containing each allele of rs7726117 (Supplemental Table 25) for allelic differences in transcriptional activity using luciferase reporter assays in HepG2 cells (López...
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Method: Estimation of allele-specific fitness effects across human protein-coding sequences and implications for disease
- Yi-Fei Huang and
- Adam Siepel
Genome Res. August 2019 29: 1310-1321; Published in Advance June 27, 2019, doi:10.1101/gr.245522.118
...), for estimating the fitness effects of all observed and potential single-nucleotide variants, based on polymorphism data and predictive genomic features. We applied LASSIE to 51 high-coverage sequences annotated with 33 genomic features and constructed a map of allele-specific selection coefficients across all...
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Research: Allele-specific control of replication timing and genome organization during development
- Juan Carlos Rivera-Mulia,
- Andrew Dimond,
- Daniel Vera,
- Claudia Trevilla-Garcia,
- Takayo Sasaki,
- Jared Zimmerman,
- Catherine Dupont,
- Joost Gribnau,
- Peter Fraser,
- and David M. Gilbert
Genome Res. June 2018 28: 800-811; Published in Advance May 7, 2018, doi:10.1101/gr.232561.117
...-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq), and chromatin accessibility (ATAC-seq). We also present HARP, a new computational tool for sorting SNPs in phased s to efficiently measure allele-specific -wide data. Analysis of six different hybrid mESC clones with different s (C57BL/6, 129...
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Research: Extensive and coordinated control of allele-specific expression by both transcription and translation in Candida albicans
- Dale Muzzey,
- Gavin Sherlock,
- and Jonathan S. Weissman
Genome Res. June 2014 24: 963-973; Published in Advance April 14, 2014, doi:10.1101/gr.166322.113
...of transcriptional control, both in cis and trans. Here we have performed the first highly sensitive, -wide, allele-specific assays of both transcription and translation in a natural organism. Though previous sequencing-based assays of allele-specific expression have been cast in doubt due to inconsistencies...
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Method: Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data
- Kaixuan Luo,
- Jianling Zhong,
- Alexias Safi,
- Linda K. Hong,
- Alok K. Tewari,
- Lingyun Song,
- Timothy E. Reddy,
- Li Ma,
- Gregory E. Crawford,
- and Alexander J. Hartemink
Genome Res. June 2022 32: 1183-1198; Published in Advance May 24, 2022, doi:10.1101/gr.272203.120
...successfully identified differential CTCF occupancy between individuals across CEU and YRI families (Fig. 6A) and was sensitive enough to capture quantitative differences in CTCF occupancy between allele genotypes at allele-specific sites within CEU and YRI families (Fig. 6B).View larger version...
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Methods: SNP-specific array-based allele-specific expression analysis
- Hans T. Bjornsson,
- Thomas J. Albert,
- Christine M. Ladd-Acosta,
- Roland D. Green,
- Michael A. Rongione,
- Christina M. Middle,
- Rafael A. Irizarry,
- Karl W. Broman,
- and Andrew P. Feinberg
Genome Res. May 2008 18: 771-779; Published in Advance March 27, 2008, doi:10.1101/gr.073254.107
..., and in these cases, the log2 ASE ratio from the plus probes is generally similar to that from the minus probes, suggesting that we are indeed measuring true allele-specific silencing. Validation by quantitative allele-specific expression reconstitution In order to determine whether ASE detection by hybridization...

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